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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate and reliable studies (Klimisch score 2) from reference substances with similar structures and intrinsic properties. Read-across is justified based on ccommon functional group, common precursors/breakdown products and similarities in physicochemical and toxicological properties (refer to endpoint discussion for further details). The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Justification for grouping of substances and read-across

There are no data available for the reproduction toxicity fatty acids, C8-10, octyl esters (CAS 91031-98-0). In order to fulfil the standard information requirements set out in Annex IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, a read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

The general rules for grouping of substances and read-across approach were followed, as laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

Overview Reproductive toxicity:

CAS#

Reproductive Toxicity

91031-98-0

RA: 123-95-5

RA: 111-62-6

123-95-5

NOAEL: 6000 mg/kg bw/day

111-62-6

NOAEL: 5500 mg/kg bw/day

 

The above-mentioned substances are considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the outcome of the same endpoints for fatty acids, C8-10, octyl esters (CAS 91031-98-0).

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

CAS 123-95-5

NOAEL (fertility) = 6000 mg/kg bw/day, non-guideline

In a non-guideline study (Smith, 1953) groups of 20 male and female Sprague-Dawley rats were treated during 10 weeks with butyl stearate (CAS 123-95-5) at a concentration of 6.25% in diet (corresponding to about 6000 mg/kg bw/day) and were then mated. F1 animals were also treated postweaning and sacrificed at day 21 post weaning. A control group of 12 male and 12 female animals of the same age were fed the basal ratio for 10 weeks and mated. The examination of parental animals was focused on fertility. The following parameters were examined in F1 offsprings: number and sex of pups, litter size, survival of offspring, body weight (daily), weight gain. No adverse effects were noted with respect to fertility in the parental animals. No adverse effects were observed with respect to litter size and survival of offspring. Only the growth during the preweaning and postweaning periods was slightly retarded. No gross lesions were observed among these animals at sacrifice at the end of the 21-day postweaning period. Therefore, a NOAEL for fertility in rats for butyl stearate was determined to be approx. 6000 mg/kg bw/day.

 

CAS 111-62-2

NOAEL (fertility) = 5500 mg/kg bw/day, OECD 408

A 90-day oral feeding study (Bookstaff, 2004) was performed with ethyl oleate (CAS 111-62-6) according to the 1993 FDA draft "Redbook II" guidelines (Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food). The study was performed equivalently to OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents) with additional assessments of oestrus cycle and sperm parameters. The purpose of the study was to determine the safety of ethyl oleate in a 91-day feeding study in Sprague-Dawley rats. Ethyl oleate was mixed into AIN-93G purified diet at levels of approx. 0, 1900, 3800 and 6000 mg/kg bw/day. All the diets were calorie- and fat-matched using high oleic safflower oil (HOSO) as the control fat. There were 20 male and 20 female rats per group. Ethyl oleate in the diet was well tolerated and there were no toxicologically significant findings in any of the measured parameters (clinical observations, body weight gains, appearance of the faeces, ophthalmic examinations, haematology, clinical chemistry, urinalysis, organ weights, histopathology, or male and female reproductive assessments). Based on the absence of abnormalities concerning oestrus cyclus, sperm characterization and histopathologic evaluation of oestrus cycle in females, sperm characterization in males and histologic examinations (incl. epididymides, mammary gland, ovaries, prostate, seminal vesicles, testes, thyroid with parathyroid, uterus with uterine horns and vagina) the subchronic 90-day oral NOAEL for fertility in rats for ethyl oleate was found to be approx. 5500 mg/kg bw/day.

Conclusion for reproduction toxicity

Two studies were available investigating the reproduction toxicity using analogue based read-across. The studies from the analogue substances butyl stearate (CAS 123-95-5) and ethyl oleate (CAS 111-62-6) did not show treatment-related effects up to the highest tested dose levels. Thus, no hazard for reproduction toxicity was identified.


Short description of key information:
No hazard for reproductive toxicity was identified for fatty acids, C8-10, octyl esters (CAS 91031-98-0).

Justification for selection of Effect on fertility via oral route:
Hazard assessment is conducted by means of read-across. The selected studies are the most adequate and reliable studies based on the identified similarities in structure and intrinsic properties and overall quality assessment (refer to the endpoint discussion for further details).

Effects on developmental toxicity

Description of key information
The NOAELs for maternal and developmental toxicity for fatty acids, C16-18, 2-ethylhexyl esters (CAS 91031-48-0) and for 2-ethyl hexyl stearate (CAS 22047-49-0) were found to be 1000 mg/kg bw/day.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate and reliable studies (Klimisch score 2) from reference substances with similar structures and intrinsic properties. Read-across is justified based on common functional group, common precursors/breakdown products and similarities in physicochemical and toxicological properties (refer to endpoint discussion for further details). The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Justification for grouping of substances and read-across

There are no data available for the reproduction toxicity fatty acids, C8-10, octyl esters (CAS 91031-98-0). In order to fulfil the standard information requirements set out in Annex IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, a read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

The general rules for grouping of substances and read-across approach were followed, as laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

 

Overview of developmental toxicity

CAS#

Developmental Toxicity

91031-98-0

RA: 22047-49-0

RA: 91031-48-0

22047-49-0

NOAEL: 1000 mg/kg bw/day

91031-48-0

NOAEL: 1000 mg/kg bw/day

 

The above-mentioned substances are considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the outcome of the same endpoints for fatty acids, C8-10, octyl esters (CAS 91031-98-0).

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

CAS 22047-49-0

NOAEL (maternal toxicity) = 1000 mg/kg bw/day, OECD 414

NOAEL (embryo-/fetotoxicity and teratogenicity) = 1000 mg/kg bw/day, OECD 414

The developmental toxicity of 2-ethylhexyl stearate (CAS 22047-49-0) was investigated according to OECD Guideline 414 and GLP conditions (Aulmann, 2000). Groups of 24 female Sprague-Dawley rats received daily oral gavage doses of the test substance in arachidis oil at dose levels of 0, 100, 300 and 1000 mg/kg bw/d during gestational days 6 to 15. On day 20 of gestation the animals were euthanized and examined for maternal and fetal parameters. Based on the number of implantations, number of total litter losses by resorption, mortality, clinical signs, body weight, gross pathology and organ weights of maternal animals the NOAEL for maternal toxicity was found to be 1000 mg/kg bw/d. Examination of fetus litter size and weights, offspring viability (number alive and number dead), sex ratio, grossly visible abnormalities, external, head, soft tissue and skeletal abnormalities showed no differences to control and no indication for teratogenic effects. Therefore, the NOAEL for embryo-/fetotoxicity and teratogenicity in rats for 2-Ethylhexyl Stearate was found to be 1000 mg/kg bw/day.

CAS 91031-48-0

NOAEL (maternal toxicity) = 1000 mg/kg bw/day, OECD 414

NOAEL (embryo-/fetotoxicity and teratogenicity) = 1000 mg/kg bw/day, OECD 414

A prenatal developmental toxicity study was performed with fatty acids, C16-18, 2-ethylhexyl esters (CAS 91031-48-0) according to OECD Guideline 414 (Pittermann, 1994). Groups of 24 female Sprague-Dawley rats received daily oral gavage doses of the test substance in arachidis oil at dose levels of 0, 100, 300 and 1000 mg/kg bw/day during gestational days 6 to 15. On day 20 of gestation the animals were euthanized and examined for maternal and fetal parameters. Based on the number of implantations, number of total litter losses by resorption, mortality, clinical signs, body weight, gross pathology and organ weights of maternal animals the NOAEL for maternal toxicity was found to be 1000 mg/kg bw/day. Examination of fetus litter size and weights, offspring viability (number alive and number dead), sex ratio, grossly visible abnormalities, external, head, soft tissue and skeletal abnormalities showed no differences to control and no indication for teratogenic effects. Therefore, the NOAEL for embryo-/fetotoxicity and teratogenicity in rats for Fatty Acids C16-18, 2-Ethylhexyl Esters was found to be 1000 mg/kg bw/day.

Conclusion for developmental toxicity

Two studies investigating the developmental toxicity are available using analogue based read-across. The studies from the analogue substances 2-ethylhexyl stearate (CAS 22047-49-0) and fatty acids, C16-18, 2-ethylhexyl esters (CAS 91031-48-0) did not show treatment-related effects up to the highest tested dose level. Thus, no hazard for developmental toxicity was identified.

 


Justification for selection of Effect on developmental toxicity: via oral route:
Hazard assessment is conducted by means of read-across. The selected studies are the most adequate and reliable studies based on the identified similarities in structure and intrinsic properties and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on read-across from the structurally similar substances, the available data on toxicity to reproduction and development do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.